Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.

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Main Authors: Pedrosa,Alano Martins, Barbosa,Maritza Cavalcante, Santos,Thayna Nogueira dos, Leal,Luzia Kalyne Almeida Moreira, Lopes,Amanda de Araújo, Elias,Darcielle Bruna Dias, Sasahara,Greyce Luri, Cavalcanti,Bruno Coêlho, Gonçalves,Romélia Pinheiro
Format: Digital revista
Language:English
Published: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas 2014
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502014000200401
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spelling oai:scielo:S1984-825020140002004012015-08-13Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyureaPedrosa,Alano MartinsBarbosa,Maritza CavalcanteSantos,Thayna Nogueira dosLeal,Luzia Kalyne Almeida MoreiraLopes,Amanda de AraújoElias,Darcielle Bruna DiasSasahara,Greyce LuriCavalcanti,Bruno CoêlhoGonçalves,Romélia Pinheiro Hydroxyurea/cytotoxicity Sickle cell anaemia/treatment Neutrophils/DNA damage Deoxyribonucleic acid/damage Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.info:eu-repo/semantics/openAccessUniversidade de São Paulo, Faculdade de Ciências FarmacêuticasBrazilian Journal of Pharmaceutical Sciences v.50 n.2 20142014-06-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502014000200401en10.1590/S1984-82502014000200020
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libraryname SciELO
language English
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author Pedrosa,Alano Martins
Barbosa,Maritza Cavalcante
Santos,Thayna Nogueira dos
Leal,Luzia Kalyne Almeida Moreira
Lopes,Amanda de Araújo
Elias,Darcielle Bruna Dias
Sasahara,Greyce Luri
Cavalcanti,Bruno Coêlho
Gonçalves,Romélia Pinheiro
spellingShingle Pedrosa,Alano Martins
Barbosa,Maritza Cavalcante
Santos,Thayna Nogueira dos
Leal,Luzia Kalyne Almeida Moreira
Lopes,Amanda de Araújo
Elias,Darcielle Bruna Dias
Sasahara,Greyce Luri
Cavalcanti,Bruno Coêlho
Gonçalves,Romélia Pinheiro
Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
author_facet Pedrosa,Alano Martins
Barbosa,Maritza Cavalcante
Santos,Thayna Nogueira dos
Leal,Luzia Kalyne Almeida Moreira
Lopes,Amanda de Araújo
Elias,Darcielle Bruna Dias
Sasahara,Greyce Luri
Cavalcanti,Bruno Coêlho
Gonçalves,Romélia Pinheiro
author_sort Pedrosa,Alano Martins
title Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
title_short Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
title_full Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
title_fullStr Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
title_full_unstemmed Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
title_sort cytotoxicity and dna damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea
description Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.
publisher Universidade de São Paulo, Faculdade de Ciências Farmacêuticas
publishDate 2014
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502014000200401
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